Interneuron

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Jeffry S. Isaacson - One of the best experts on this subject based on the ideXlab platform.

  • from dendrite to soma dynamic routing of inhibition by complementary Interneuron microcircuits in olfactory cortex
    Neuron, 2010
    Co-Authors: Caleb C A Stokes, Jeffry S. Isaacson
    Abstract:

    Summary Diverse inhibitory pathways shape cortical information processing; however, the relevant Interneurons recruited by sensory stimuli and how they impact principal cells are unclear. Here we show that two major Interneuron circuits govern dynamic inhibition in space and time within the olfactory cortex. Dendritic-targeting layer 1 Interneurons receive strong input from the olfactory bulb and govern early-onset feedforward inhibition. However, this circuit is only transiently engaged during bursts of olfactory bulb input. In contrast, somatic-targeting layer 3 Interneurons, recruited exclusively by recurrent excitation from pyramidal cells, produce late-onset feedback inhibition. Our results reveal two complementary Interneuron circuits enforcing widespread inhibition, which shifts from the apical dendrites to somata of pyramidal cells during bursts of sensory input.

  • From Dendrite to Soma: Dynamic Routing of Inhibition by Complementary Interneuron Microcircuits in Olfactory Cortex
    Neuron, 2010
    Co-Authors: Caleb C A Stokes, Jeffry S. Isaacson
    Abstract:

    Diverse inhibitory pathways shape cortical information processing; however, the relevant Interneurons recruited by sensory stimuli and how they impact principal cells are unclear. Here we show that two major Interneuron circuits govern dynamic inhibition in space and time within the olfactory cortex. Dendritic-targeting layer 1 Interneurons receive strong input from the olfactory bulb and govern early-onset feedforward inhibition. However, this circuit is only transiently engaged during bursts of olfactory bulb input. In contrast, somatic-targeting layer 3 Interneurons, recruited exclusively by recurrent excitation from pyramidal cells, produce late-onset feedback inhibition. Our results reveal two complementary Interneuron circuits enforcing widespread inhibition, which shifts from the apical dendrites to somata of pyramidal cells during bursts of sensory input. © 2010 Elsevier Inc.

Peter Jonas - One of the best experts on this subject based on the ideXlab platform.

  • asynchronous gaba release generates long lasting inhibition at a hippocampal Interneuron principal neuron synapse
    Nature Neuroscience, 2005
    Co-Authors: Stefan Hefft, Peter Jonas
    Abstract:

    Hippocampal GABAergic Interneurons show diverse molecular and morphological properties. The functional significance of this diversity for information processing is poorly understood. Here we show that cholecystokinin (CCK)-expressing Interneurons in rat dentate gyrus release GABA in a highly asynchronous manner, in contrast to parvalbumin (PV) Interneurons. With a gamma-frequency burst of ten action potentials, the ratio of asynchronous to synchronous release is 3:1 in CCK Interneurons but is 1:5 in parvalbumin Interneurons. N-type channels trigger synchronous and asynchronous release in CCK Interneuron synapses, whereas P/Q-type Ca2+ channels mediate release at PV Interneuron synapses. Effects of Ca2+ chelators suggest that both a long-lasting presynaptic Ca2+ transient and a large distance between Ca2+ source and sensor of exocytosis contribute to the higher ratio of asynchronous to synchronous release in CCK Interneuron synapses. Asynchronous release occurs at physiological temperature and with behaviorally relevant stimulation patterns, thus generating long-lasting inhibition in the brain.

  • Interneuron diversity series fast in fast out temporal and spatial signal processing in hippocampal Interneurons
    Trends in Neurosciences, 2004
    Co-Authors: Peter Jonas, Josef Bischofberger, Desdemona Fricker, Richard B Miles
    Abstract:

    Abstract The operation of neuronal networks crucially depends on a fast time course of signaling in inhibitory Interneurons. Synapses that excite Interneurons generate fast currents, owing to the expression of glutamate receptors of specific subunit composition. Interneurons generate brief action potentials in response to transient synaptic activation and discharge repetitively at very high frequencies during sustained stimulation. The ability to generate short-duration action potentials at high frequencies depends on the expression of specific voltage-gated K + channels. Factors facilitating fast action potential initiation following synaptic excitation include depolarized Interneuron resting potential, subthreshold conductances and active dendrites. Finally, GABA release at Interneuron output synapses is rapid and highly synchronized, leading to a faster inhibition in postsynaptic Interneurons than in principal cells. Thus, the expression of distinct transmitter receptors and voltage-gated ion channels ensures that Interneurons operate with high speed and temporal precision.

  • Interneuron Diversity series: Fast in, fast out – temporal and spatial signal processing in hippocampal Interneurons
    Trends in Neurosciences, 2004
    Co-Authors: Peter Jonas, Josef Bischofberger, Desdemona Fricker, Richard B Miles
    Abstract:

    Abstract The operation of neuronal networks crucially depends on a fast time course of signaling in inhibitory Interneurons. Synapses that excite Interneurons generate fast currents, owing to the expression of glutamate receptors of specific subunit composition. Interneurons generate brief action potentials in response to transient synaptic activation and discharge repetitively at very high frequencies during sustained stimulation. The ability to generate short-duration action potentials at high frequencies depends on the expression of specific voltage-gated K + channels. Factors facilitating fast action potential initiation following synaptic excitation include depolarized Interneuron resting potential, subthreshold conductances and active dendrites. Finally, GABA release at Interneuron output synapses is rapid and highly synchronized, leading to a faster inhibition in postsynaptic Interneurons than in principal cells. Thus, the expression of distinct transmitter receptors and voltage-gated ion channels ensures that Interneurons operate with high speed and temporal precision.

  • distal initiation and active propagation of action potentials in Interneuron dendrites
    Science, 2000
    Co-Authors: Marco Martina, Imre Vida, Peter Jonas
    Abstract:

    Fast and reliable activation of inhibitory Interneurons is critical for the stability of cortical neuronal networks. Active conductances in dendrites may facilitate Interneuron activation, but direct experimental evidence was unavailable. Patch-clamp recordings from dendrites of hippocampal oriens-alveus Interneurons revealed high densities of voltage-gated sodium and potassium ion channels. Simultaneous recordings from dendrites and somata suggested that action potential initiation occurs preferentially in the axon with long threshold stimuli, but can be shifted to somatodendritic sites when brief stimuli are applied. After initiation, action potentials propagate over the somatodendritic domain with constant amplitude, high velocity, and reliability, even during high-frequency trains.

  • submillisecond ampa receptor mediated signaling at a principal neuron Interneuron synapse
    Neuron, 1997
    Co-Authors: Jorg R P Geiger, Joachim H R Lubke, Arnd Roth, Michael Frotscher, Peter Jonas
    Abstract:

    Abstract Glutamatergic transmission at a principal neuron–Interneuron synapse was investigated by dual whole-cell patch-clamp recording in rat hippocampal slices combined with morphological analysis. Evoked EPSPs with rapid time course (half duration ≈ 4 ms; 34°C) were generated at multiple synaptic contacts established on the Interneuron dendrites close to the soma. The underlying postsynaptic conductance change showed a submillisecond rise and decay, due to the precise timing of glutamate release and the rapid deactivation of the postsynaptic AMPA receptors. Simulations based on a compartmental model of the Interneuron indicated that the rapid postsynaptic con-ductance change determines the shape and the somatodendritic integration of EPSPs, thus enabling Interneurons to detect synchronous principal neuron activity.

Caleb C A Stokes - One of the best experts on this subject based on the ideXlab platform.

  • from dendrite to soma dynamic routing of inhibition by complementary Interneuron microcircuits in olfactory cortex
    Neuron, 2010
    Co-Authors: Caleb C A Stokes, Jeffry S. Isaacson
    Abstract:

    Summary Diverse inhibitory pathways shape cortical information processing; however, the relevant Interneurons recruited by sensory stimuli and how they impact principal cells are unclear. Here we show that two major Interneuron circuits govern dynamic inhibition in space and time within the olfactory cortex. Dendritic-targeting layer 1 Interneurons receive strong input from the olfactory bulb and govern early-onset feedforward inhibition. However, this circuit is only transiently engaged during bursts of olfactory bulb input. In contrast, somatic-targeting layer 3 Interneurons, recruited exclusively by recurrent excitation from pyramidal cells, produce late-onset feedback inhibition. Our results reveal two complementary Interneuron circuits enforcing widespread inhibition, which shifts from the apical dendrites to somata of pyramidal cells during bursts of sensory input.

  • From Dendrite to Soma: Dynamic Routing of Inhibition by Complementary Interneuron Microcircuits in Olfactory Cortex
    Neuron, 2010
    Co-Authors: Caleb C A Stokes, Jeffry S. Isaacson
    Abstract:

    Diverse inhibitory pathways shape cortical information processing; however, the relevant Interneurons recruited by sensory stimuli and how they impact principal cells are unclear. Here we show that two major Interneuron circuits govern dynamic inhibition in space and time within the olfactory cortex. Dendritic-targeting layer 1 Interneurons receive strong input from the olfactory bulb and govern early-onset feedforward inhibition. However, this circuit is only transiently engaged during bursts of olfactory bulb input. In contrast, somatic-targeting layer 3 Interneurons, recruited exclusively by recurrent excitation from pyramidal cells, produce late-onset feedback inhibition. Our results reveal two complementary Interneuron circuits enforcing widespread inhibition, which shifts from the apical dendrites to somata of pyramidal cells during bursts of sensory input. © 2010 Elsevier Inc.

Gordon Fishell - One of the best experts on this subject based on the ideXlab platform.

  • early somatostatin Interneuron connectivity mediates the maturation of deep layer cortical circuits
    Neuron, 2016
    Co-Authors: Sebnem N Tuncdemir, Brie Wamsley, Floor J Stam, Fumitaka Osakada, Martyn Goulding, Edward M Callaway, Bernardo Rudy, Gordon Fishell
    Abstract:

    The precise connectivity of somatostatin and parvalbumin cortical Interneurons is generated during development. An understanding of how these Interneuron classes incorporate into cortical circuitry is incomplete but essential to elucidate the roles they play during maturation. Here, we report that somatostatin Interneurons in infragranular layers receive dense but transient innervation from thalamocortical afferents during the first postnatal week. During this period, parvalbumin Interneurons and pyramidal neurons within the same layers receive weaker thalamocortical inputs, yet are strongly innervated by somatostatin Interneurons. Further, upon disruption of the early (but not late) somatostatin Interneuron network, the synaptic maturation of thalamocortical inputs onto parvalbumin Interneurons is perturbed. These results suggest that infragranular somatostatin Interneurons exhibit a transient early synaptic connectivity that is essential for the establishment of thalamic feedforward inhibition mediated by parvalbumin Interneurons.

  • Interneuron cell types are fit to function
    Nature, 2014
    Co-Authors: Adam Kepecs, Gordon Fishell
    Abstract:

    Understanding brain circuits begins with an appreciation of their component parts — the cells. Although GABAergic Interneurons are a minority population within the brain, they are crucial for the control of inhibition. Determining the diversity of these Interneurons has been a central goal of neurobiologists, but this amazing cell type has so far defied a generalized classification system. Interneuron complexity within the telencephalon could be simplified by viewing them as elaborations of a much more finite group of developmentally specified cardinal classes that become further specialized as they mature. Our perspective emphasizes that the ultimate goal is to dispense with classification criteria and directly define Interneuron types by function.

  • Specification of GABAergic Neocortical Interneurons
    Cortical Development, 2013
    Co-Authors: Goichi Miyoshi, Robert P Machold, Gordon Fishell
    Abstract:

    Inhibitory GABAergic Interneurons within the cerebral cortex are critical for fine-tuning the activity of cortical circuits and thus are thought to be involved in generating the distinct oscillatory patterns that underlie higher brain functions such as consciousness and memory. Understanding how cortical Interneurons are specified during development is important not just from the standpoint of basic research but also is likely to provide key insights into how cognitive disorders emerge. Although Interneurons only consist of around 20 % of the neurons within the neocortex, they are extremely diverse with regard to their morphologies, molecular expression profiles, intrinsic electrophysiological properties, and synaptic connections. In rodents, most neocortical Interneurons originate during embryogenesis from ventrally located structures, primarily the ganglionic eminences, and therefore must migrate over long distances following discrete pathways to reach the appropriate cortical areas. Thus, proper coordination of the distinct migration programs followed by pyramidal cells and Interneuron precursors during development is crucial for the assembly of functional microcircuits within the cerebral cortex. Here, we review and discuss emerging views of how cortical GABAergic Interneuron specification, migration, and integration occur from embryonic to early postnatal stages.

  • neuronal activity is required for the development of specific cortical Interneuron subtypes
    Nature, 2011
    Co-Authors: Natalia V De Marco Garcia, Theofanis Karayannis, Gordon Fishell
    Abstract:

    Interneurons migrate long distances before settling into a specific microcircuit. Because these cells are known to participate in correlated network activity, it is possible that electrical inputs may influence migration and integration. By manipulating neuronal activity in subsets of developing Interneurons, Fishell and colleagues find that proper migration does indeed depend on this activity, involving a transcription-factor signalling pathway specific to those Interneuron cell types. Electrical activity has been shown to regulate development in a variety of species and in various structures1, including the retina2,3,4, spinal cord5,6 and cortex5. Within the mammalian cortex specifically, the development of dendrites and commissural axons in pyramidal cells is activity-dependent7,8. However, little is known about the developmental role of activity in the other major cortical population of neurons, the GABA-producing Interneurons. These neurons are morphologically and functionally heterogeneous and efforts over the past decade have focused on determining the mechanisms that contribute to this diversity9,10,11. It was recently discovered that 30% of all cortical Interneurons arise from a relatively novel source within the ventral telencephalon, the caudal ganglionic eminence (CGE)11,12. Owing to their late birth date, these Interneurons populate the cortex only after the majority of other Interneurons and pyramidal cells are already in place and have started to functionally integrate. Here we demonstrate in mice that for CGE-derived reelin (Re)-positive and calretinin (Cr)-positive (but not vasoactive intestinal peptide (VIP)-positive) Interneurons12,13, activity is essential before postnatal day 3 for correct migration, and that after postnatal day 3, glutamate-mediated activity controls the development of their axons and dendrites. Furthermore, we show that the engulfment and cell motility 1 gene (Elmo1)14, a target of the transcription factor distal-less homeobox 1 (Dlx1)15, is selectively expressed in Re+ and Cr+ Interneurons and is both necessary and sufficient for activity-dependent Interneuron migration. Our findings reveal a selective requirement for activity in shaping the cortical integration of specific neuronal subtypes.

  • the requirement of nkx2 1 in the temporal specification of cortical Interneuron subtypes
    Neuron, 2008
    Co-Authors: Simon J B Butt, Vitor H Sousa, Goichi Miyoshi, Jens Hjerlingleffler, Marc V Fuccillo, Shioko Kimura, Gordon Fishell
    Abstract:

    Summary Previous work has demonstrated that the character of mouse cortical Interneuron subtypes can be directly related to their embryonic temporal and spatial origins. The relationship between embryonic origin and the character of mature Interneurons is likely reflected by the developmental expression of genes that direct cell fate. However, a thorough understanding of the early genetic events that specify subtype identity has been hampered by the perinatal lethality resulting from the loss of genes implicated in the determination of cortical Interneurons. Here, we employ a conditional loss-of-function approach to demonstrate that the transcription factor Nkx2-1 is required for the proper specification of specific Interneuron subtypes. Removal of this gene at distinct neurogenic time points results in a switch in the subtypes of neurons observed at more mature ages. Our strategy reveals a causal link between the embryonic genetic specification by Nkx2-1 in progenitors and the functional attributes of their neuronal progeny in the mature nervous system.

Adam Kepecs - One of the best experts on this subject based on the ideXlab platform.

  • Interneuron types as attractors and controllers
    Annual Review of Neuroscience, 2020
    Co-Authors: Gord Fishell, Adam Kepecs
    Abstract:

    Cortical Interneurons display striking differences in shape, physiology, and other attributes, challenging us to appropriately classify them. We previously suggested that Interneuron types should b...

  • Interneuron cell types are fit to function
    Nature, 2014
    Co-Authors: Adam Kepecs, Gordon Fishell
    Abstract:

    Understanding brain circuits begins with an appreciation of their component parts — the cells. Although GABAergic Interneurons are a minority population within the brain, they are crucial for the control of inhibition. Determining the diversity of these Interneurons has been a central goal of neurobiologists, but this amazing cell type has so far defied a generalized classification system. Interneuron complexity within the telencephalon could be simplified by viewing them as elaborations of a much more finite group of developmentally specified cardinal classes that become further specialized as they mature. Our perspective emphasizes that the ultimate goal is to dispense with classification criteria and directly define Interneuron types by function.